Application of antiCD19 CAR T lymphocytes for the treatment of adult patients with B-cell acute lymphoblastic leukemia. Phase I/II clinical trial (MERMAID1)

Phase 1

• Conditions: Relapsed and refractory B-cell Acute Lymphoblastic Leukemia (B-ALL); MedDRA version: 21.1Level: LLTClassification code 10066109Term: Precursor B-lymphoblastic leukemia acuteSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-003409-23-PL
• Lead Sponsor: Medical University of Warsaw

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-05-31
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Diagnosis of B-ALL Ph (-) with confirmed expression of CD19 molecules in> 90% of neoplastic cells after resistance / relapse;
2. Primary refractory disease, i.e. complete remission (CR or CRi) has not been achieved after 2 cycles of induction chemotherapy or
3. Recurrent disease - when:
A. complete remission was achieved, but the disease relapsed (> 5% B-ALL lymphoblasts in the bone marrow)
B. complete remission of MRD (+) was achieved, but after at least 2 chemotherapy cycles (counting from the start of treatment) MRD progressed (cytometric method) by min. 1 log in 2 consecutive bone marrow biopsies taken at an interval of min. 2 weeks;
4. Age 18-65 years on screening date;
5. Performance status assessed in the ECOG (Eastern Cooperative Oncology Group) scale of = 2,
6. Satisfactory organ function during screening:
A. ALT / AST activity <2.5 x Upper Limit of Normal (ULN) and total bilirubin <1.5 mg / dL (<4 mg / dL in patients with Gilbert's syndrome);
B. Ejection fraction (EF)> 40% confirmed by ECHO, with no significant pericardial effusion within 6 weeks prior to screening;
C. Respiratory capacity: arterial blood saturation> 92% without oxygen therapy, no significant pleural effusion;
D. Creatinine clearance> 30 ml / min;
7. Negative test results for HIV, HBV (HBs-) and HCV (anti-HCV-);
8. Understanding and giving informed consent to participate in the study,
9. Negative pregnancy test (serum) in women of childbearing age;
10. Declaration of the use of an appropriate method of contraception after signing the informed consent form up to 6 months from the use of CAR T therapy;
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Diagnosis of B-cell lymphoblastic lymphoma (presence of <20% leukemic blasts in blood or bone marrow at diagnosis);
2. Isolated central nervous system (CNS) relapse;
3. History of significant diseases of the central nervous system (CNS) or significant current CNS disorders (seizures, paralysis, aphasia, CNS ischemia / hemorrhage, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, psychosis and diseases associated with incoordination or movement disorders);
4. The need for systemic immunosuppressive therapy;
5. Allogeneic hematopoietic cells (alloHCT) transplant surgery in less than 3 months prior to screening;
6. Presence of Philadelphia chromosome in cytogenetic test or BCR-ABL transcript in FISH or molecular test;
7. Concurrent presence of another neoplasm and another neoplasm diagnosed up to 2 years prior to study enrollment;
8. Active bacterial, viral or fungal infections, including SARS-CoV2;
9. Latent infections with HCV, HBV, HIV;
10. Other co-morbidities that have been assessed as likely to interfere with the conduct of the study, as assessed by the investigator;
11. Pregnancy;
12. Nursing women or women of childbearing age or men who do not consent to the use of an effective method of contraception while participating in the study;
13. Inability to give informed consent to participate in a study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified